Comparing single versus multiple virus detection in pediatric acute gastroenteritis postimplementation of routine multiplex RT-PCR diagnostic testing.

Utilizing multiplex real time polymerase chain reaction (RT-PCR) for rapid diagnosis of gastroenteritis, enables simultaneous detection of multiple pathogens. A comparative analysis of disease characteristics was conducted between cases with single and multiple viruses. Rotavirus vaccine was introduced in 2010, reaching a 70% coverage in 2 years. All rectal swabs collected from diarrheic children (<5 years) between December 2017 and March 2022 were included. Detection of the same viruses within 2 months was considered a single episode. Episodes with positive stool bacterial PCR were excluded. A total of 5879 samples were collected, revealing 86.9% (1509) with single virus detection and 13.1% (227) with multiple viruses. The most frequent combination was rotavirus and norovirus (27.8%), these infections followed a winter-spring seasonality akin to rotavirus. Children with multivirus infections exhibited higher immunodeficiency (OR 2.06) rates, but lower food allergy (OR 0.45) and prematurity rates (OR 0.55) compared to single infections. Greater disease severity, evaluated by the Vesikari score, was observed in multivirus episodes (p < 0.001, OR 1.12). Multivirus infections accounted for 13.1% of symptomatic cases in hospitalized young children. Despite vaccination efforts, rotavirus remained prominent, frequently in co-infections with norovirus. Overall, multivirus infections were linked to more severe diseases than single virus cases.

Age-Dependent Reduction in Asthmatic Pathology through Reprogramming of Postviral Inflammatory Responses.

Asthma is a chronic disease of childhood, but for unknown reasons, disease activity sometimes subsides as children mature. In this study, we present clinical and animal model evidence suggesting that the age dependency of childhood asthma stems from an evolving host response to respiratory viral infection. Using clinical data, we show that societal suppression of respiratory virus transmission during coronavirus disease 2019 lockdown disrupted the traditional age gradient in pediatric asthma exacerbations, connecting the phenomenon of asthma remission to virus exposure. In mice, we show that asthmatic lung pathology triggered by Sendai virus (SeV) or influenza A virus is highly age-sensitive: robust in juvenile mice (4-6 wk old) but attenuated in mature mice (>3 mo old). Interestingly, allergen induction of the same asthmatic traits was less dependent on chronological age than viruses. Age-specific responses to SeV included a juvenile bias toward type 2 airway inflammation that emerged early in infection, whereas mature mice exhibited a more restricted bronchiolar distribution of infection that produced a distinct type 2 low inflammatory cytokine profile. In the basal state, aging produced changes to lung leukocyte burden, including the number and transcriptional landscape of alveolar macrophages (AMs). Importantly, depleting AMs in mature mice restored post-SeV pathology to juvenile levels. Thus, aging influences chronic outcomes of respiratory viral infection through regulation of the AM compartment and type 2 inflammatory responses to viruses. Our data provide insight into how asthma remission might develop in children.

Neonatal diagnosis of primary ciliary dyskinesia in a high consanguinity population: a single tertiary center experience.

Though PCD usually presents after birth in term neonates, diagnosing PCD during the neonatal and infancy stages is uncommon, particularly in children who do not exhibit laterality defects. We report our recent experience with the diagnosis of PCD in the neonatal and early infantile period in a highly consanguine population. This was achieved by implementing a novel genetic-based diagnostic approach based on direct testing for recognized regional genetic variants. We conducted a retrospective analysis of children diagnosed with PCD at Soroka University Medical Center during the neonatal or early infantile period between 2020 and 2023. We included children under 3 months of age who had a genetic confirmation of PCD, as evidenced by the presence of two pathogenic variants in recognized genes. Genetic testing targeted regional genetic variants in previously identified PCD genes. Eight patients were included. The median age at diagnosis was 12.5 days. Three (38%) were born prematurely < 34 weeks gestational age. All patients were presented with respiratory distress and hypoxemia after birth. The median duration of oxygen support was 23 days, and upper lobe atelectasis was present in five patients (63%). Congenital cardiac malformation was present in four patients. Organ laterality defects were present in four patients. Genetic mutations identified were in the DNAAF5, DNAL1, DNAAF3, and DNAH1 genes.     Conclusion: Neonatal diagnosis of PCD is uncommon, especially in atypical presentations such as children without laterality defects or preterms. Focusing on a genetic diagnosis of the local tribal pathogenic variants promotes a potential cost-efficient test leading to earlier diagnosis. There is a need for a standardized protocol for earlier diagnosis of PCD in high-consanguinity areas. What is Known: • Primary ciliary dyskinesia (PCD) typically presents after birth in term neonates. • Diagnosing PCD during neonatal and infancy stages is challenging, particularly in children without laterality defects. What is New: • A novel genetic-based diagnostic approach was implemented on the neonatal population in a highly consanguine community, focusing on direct testing for regional genetic variants, leading to early and rapid diagnosis of PCD.

Markers for severe disease and long-term sequelae in pediatric patients with severe acute respiratory syndrome coronavirus 2 infection.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has resulted in substantial global morbidity and mortality since late 2019. Children can be infected but the disease predominantly affects adults, and research into the acute and chronic sequelae mostly pertains to this population. This study determines the clinical and demographic parameters associated with severe acute disease and chronic complications from COVID-19 in the pediatric population. METHODS: A retrospective chart review was undertaken of all patients between birth and 21 years of age who were positive for SARS-CoV-2 by polymerase chain reaction (PCR) and were admitted to two tertiary care hospitals between March 1, 2020, and January 21, 2021. Markers for severe disease were defined as supplemental oxygen requirement, positive pressure ventilation, and acute chest radiograph abnormality at presentation. Chronic disease was defined as symptoms persisting >4 weeks. RESULTS: Review of 101 patients with positive SARS-CoV2 testing found 67 presentations consistent with acute symptomatic infection. Age distribution was bimodal, with predominance in infancy and adolescence. Most (75%) had an extrapulmonary comorbidity, and fewer patients (33%) had pre-existing lung disease. A history of pulmonary comorbidity and obesity was significantly associated with markers for severe disease. Long-term chronic complications were associated with history of underlying lung disease and acute severe COVID-19. CONCLUSIONS: Demographic and clinical markers were associated with severe COVID-19 in children. Moreover, both the presence of pulmonary comorbidity and severe acute COVID-19 are associated with long-term sequelae.

B4GALT1-congenital disorders of glycosylation: Expansion of the phenotypic and molecular spectrum and review of the literature.

A congenital disorder of glycosylation due to biallelic mutations in B4GALT1 has been previously reported in only three patients with two different mutations. Through homozygosity mapping followed by segregation analysis in an extended pedigree, we identified three additional patients homozygous for a novel mutation in B4GALT1, expanding the phenotypic spectrum of the disease. The patients showed a uniform clinical presentation with intellectual disability, marked pancytopenia requiring chronic management, and novel features including pulmonary hypertension and nephrotic syndrome. Notably, affected individuals exhibited a moderate elevation of Man3GlcNAc4Fuc1 on serum N-glycan analysis, yet two of the patients had a normal pattern of transferrin glycosylation in repeated analysis. The novel mutation is the third disease-causing variant described in B4GALT1, and the first one within its transmembrane domain.

Central venous catheter-associated bloodstream infections in children diagnosed with intestinal failure in Southern Israel.

OBJECTIVES: To study the clinical, epidemiological, and microbiological associations between intestinal failure (IF) and central line-associated infections (CLABSI) in patients with central vein catheters (CVCs) during 2005-2016. METHODS: We compared retrospectively CLABSI rates according to background disease, type of line access, pathogen distribution, and antibiotic susceptibilities. RESULTS: One hundred and fourteen children (64.1% < 4 years) were enrolled. Main diagnoses were persistent diarrhea (20, 17.5%), short bowel syndrome (13, 11.4%), continuous-TPN w/o diarrhea (11, 9.7%), very early-onset inflammatory bowel disease (VEO-IBD, 8, 7%), Hirschsprung's disease (3, 2.6%), non-oncologic hematologic conditions (13, 11.4%), and other diseases (46, 40.4%). 152.749 catheter days were recorded; 71.1% had Hickman's catheters. Two hundred and nine CLABSI episodes were recorded in 58 patients (82% with IF, 13.7 and 8.2/1000 catheter days in IF, and non-gastrointestinal conditions, P = 0.09). More CLABSI were recorded in continuous TPN vs. VEO-IBD or persistent diarrhea (38.8 vs.15.8 and 12.8/1000 catheter days, P < 0.004). Among patients with Hickman in jugular vein, highest CLBSI incidence was in continuous TPN, VEO-IBD, and persistent diarrhea (29.9, 15.84, and 12.49 episodes/1000 catheter days, respectively). CVCs were removed in 38.8% CLABSI. Two hundred and thirty-five pathogens were isolated (Enterobacteriaceae spp. in 39% of IF patients, mostly in persistent diarrhea and short bowel syndrome patients, 47.6% and 34.8%, respectively). Coagulase-negative Staphylococcus was the commonest pathogen in continuous TPN, VEO-IBD, and Hirschsprung's (71.4%, 55.6% and 46.1%, respectively). CONCLUSIONS: CLABSI rates in IF patients were among the highest reported. We reported a "hierarchy" in CLABSI incidence among patients with IF and showed that CLABSI incidence and etiology were different as function of background diseases and CVC insertion site.

Maternal Education Is Inversely Related to Vaccination Delay among Infants and Toddlers.

OBJECTIVE: To determine the association between parents' level of education and delay in vaccination among infants and toddlers. STUDY DESIGN: A case-control study done in 2015-2016. Charts of 2- to 4-year-old children vaccinated in 5 neighborhood Maternal-Child Health Centers (MCHCs) in southern Israel were examined for demographic variables. Five vaccination opportunities between age 7 months and 18 months were selected to test for delays. In each MCHC, children vaccinated at the longest time-period after planned vaccination dose (fifth quintile) were compared with those vaccinated during the middle quintile. Using this relative delay approach rather than absolute delay approach permitted us to adjust the findings to the prevailing environmental and to cultural and programmatic variations between the various neighborhoods. Each of the planned vaccination visits and overall, demographic and health behavior-related variables that were significantly associated to delays by univariate analysis were tested by multivariate analysis and further adjusted by using stepwise logistic regression, using goodness of fit measures. RESULTS: Data for 2072 subjects were collected (398-426 per MCHC). Fathers' education was not associated with delays. In contrast, mothers' education was inversely associated with the probability of vaccination delay by 4%-9% (depending on the vaccination visit) for each year of schooling beyond 10 years. CONCLUSION: Using the relative delay approach, we demonstrated that maternal education, measured by schooling years, was independently inversely associated with risk of vaccination delay. This suggests that education can be regarded as an important positive component of the overall disease prevention planning at national and global levels.

Urinary tract infection in young infants discharged from the emergency room with normal urinalysis.

AIM: We describe the clinical, microbiologic, therapeutic, and outcome characteristics of infants under three months of age with a positive urine culture reported after discharge from emergency department with normal urinalysis. METHODS: We enrolled all infants with a urine culture obtained during an emergency room visit during 2004-2012, discharged without antibiotic therapy and subsequently reported with a positive urine culture. RESULTS: Three hundred and ninety-three positive urine cultures were reported; 46/393 (11.7%, 42 in patients under two months of age) had positive urine cultures following normal urinalysis at first visit. Fifteen (33%) had positive urine cultures at second visit; 11/15 (73%) infants with second positive urine culture were under one month of age, eight were asymptomatic and seven had mild symptoms at second visit. Pathogens isolated in all 15 infants were identical between first and second visit. All 27 infants re-examined at second visit at the emergency room were hospitalised, completed sepsis work/up and received antibiotic treatment. None developed serious bacterial infections. CONCLUSION: We propose a new management approach for young infants with normal urinalysis and positive urine culture and suggest restricting the management option including hospitalisation, sepsis work/up and antibiotic treatment at second visit only to infants under one month of age.

Performance of risk stratification criteria in the management of febrile young infants younger than three months of age.

AIM: We evaluated the diagnosis, risk stratification and management of febrile infants under three months of age who presented to an Israeli paediatric emergency room (ER). METHODS: This retrospective study enrolled all febrile infants examined in the paediatric ER of Soroka Medical Center during 2010-2013. The patients were classified into low-risk and high-risk subgroups and compared by age and ethnicity. RESULTS: Overall, 2251 febrile infants (60.5% of Bedouin and 34.4% of Jewish ethnicity) were enrolled. Hospitalisation rates were higher among Bedouin vs. Jewish infants (55 vs. 39.8%, p < 0.001). Fever without localising signs was diagnosed in 1028 (45.6%) infants and 499 (48.5%) were hospitalised; 26% were stratified as high-risk and 74% as low-risk. Bedouin infants rates were more likely to be at high-risk (p = 0.001) and hospitalised (p < 0.001) than Jewish infants. With regard to low-risk infants, the incidence rates were higher before two months than two to three months of age (73.3 vs. 59%, p < 0.001), as were the hospitalisation rates (46.3 vs. 20.1%, p < 0.001). No differences were recorded for the hospitalisation rates of Bedouin and Jewish infants between the three daily shifts. CONCLUSION: Major differences were recorded in hospitalisation rates, risk stratification and management of Bedouin and Jewish infants with fever without localising signs.

Seasonality of both bacteremic and nonbacteremic pneumonia coincides with viral lower respiratory tract infections in early childhood, in contrast to nonpneumonia invasive pneumococcal disease, in the pre-pneumococcal conjugate vaccine era.

We assessed the seasonality of viral lower respiratory tract infections (V-LRI), bacteremic pneumonia, nonbacteremic pneumonia and nonpneumonia invasive pneumococcal diseases (IPD) in the pre-PCV era. Both bacteremic and nonbacteremic pneumonia seasonality peaked in winter, coinciding with V-LRI seasonality, whereas non-pneumonia IPD peaked in autumn before V-LRI increase, suggesting different pathogenesis.

Clinical and laboratory parameter dynamics as markers of blood stream infections in pediatric oncology patients with fever and neutropenia.

BACKGROUND: Identifying markers associated with blood stream infection (BSI) in children with fever and neutropenia (FN) could lead to a substantial reduction in unnecessary treatment. STUDY OBJECTIVE: The aim of this study was to determine the association between clinical/laboratory parameters and BSI in pediatric oncology patients with FN. METHODS: This prospective study was conducted between 2007 and 2010 at the Pediatric oncology unit. Clinical and laboratory parameters were obtained from all hospitalized FN patients. Linear regression and trends were calculated to determine the association between clinical/laboratory parameters and BSI. RESULTS: Of the 195 FN episodes in 73 children, BSIs were identified in 38 (19%) episodes. Gram-positive bacteria, gram-negative bacteria, and fungi caused 47%, 43%, and 10% of all BSIs, respectively. Mean fever duration was longer in the BSI group (5 d) compared with the non-BSI group (2 d, P=0.01). Mean (±SD) monocyte count at admission was lower in the BSI group compared with the non-BSI group (0.06±0.1 vs. 0.14±0.33 cells/mm, respectively, P=0.05). Mean C-reactive protein (CRP) levels at hospitalization days 5 to 8 were higher in children with BSI (P<0.001). Increment trends of monocyte and platelet levels and decrement trend of CRP levels were noted in the BSI group but not in the non-BSI group (P<0.01 for all). CONCLUSIONS: Prolonged fever, lower monocyte count at admission, higher CRP levels between the fifth and the eighth hospitalization days, increment trends of monocyte and platelet levels, and CRP level decrement were associated with BSI. These factors may serve as markers for BSI in pediatric oncology patients with FN.

Circadian immunity from bench to bedside: a practical guide.

The immune system is built to counteract unpredictable threats, yet it relies on predictable cycles of activity to function properly. Daily rhythms in immune function are an expanding area of study, and many originate from a genetically based timekeeping mechanism known as the circadian clock. The challenge is how to harness these biological rhythms to improve medical interventions. Here, we review recent literature documenting how circadian clocks organize fundamental innate and adaptive immune activities, the immunologic consequences of circadian rhythm and sleep disruption, and persisting knowledge gaps in the field. We then consider the evidence linking circadian rhythms to vaccination, an important clinical realization of immune function. Finally, we discuss practical steps to translate circadian immunity to the patient's bedside.

The impact of maternal hyperemesis gravidarum on early childhood respiratory morbidity.

BACKGROUND: Lung maldevelopment due to in-utero events may potentially cause respiratory morbidity during childhood. Maternal nutritional status during pregnancy is critical for lung development. This study is contributing to the understanding of the interplay between maternal nutrition status during pregnancy, fetal lung development and the risk for respiratory diseases in early life. RESEARCH QUESTION: To investigate the association between maternal hyperemesis gravidarum (HG) during pregnancy and respiratory morbidity in the offspring's early childhood. STUDY DESIGN AND METHODS: This is a retrospective population-based cohort study that included all singleton term deliveries at Soroka University Medical Center (SUMC) between 1991 and 2021. Preterm deliveries (<37 gestational week), perinatal deaths, multiple gestations, and children with congenital malformations or chromosomal abnormalities were excluded. The main outcomes measured were offspring's hospitalizations due to pneumonia, acute bronchiolitis, asthma, or wheezing. RESULTS: Overall 232,476 deliveries were included in the study, of which 3227 women (1.4%) were diagnosed with HG. Offspring in the HG group exhibited significantly higher rates of respiratory morbidity, including asthma (OR = 1.36, 95% CI 1.22-1.36, p < .001), acute bronchiolitis (OR = 1.38, 95% CI 1.21-1.59, p < .001), and pneumonia (OR = 1.2, 95% CI 1.12-1.48, p < .001). An inverse correlation between multivariate adjusted-hazard ratios for asthma and pneumonia with offspring's age was noted. INTERPRETATION: This study provides evidence of a potential association between maternal HG during pregnancy and increased risk of respiratory morbidity in offspring's early childhood. Maternal nutritional status during pregnancy plays a crucial role in lung development, affecting respiratory health in childhood.

Diagnostic Yield of Critical Sample and Elective Fast-Test in Children After a Hypoglycemic Event: Experience From a Single Center in Israel.

OBJECTIVE: To determine the diagnostic yield of the critical sample and fast-tests as dynamic function tests for the work-up of hypoglycemia in children. METHODS: A retrospective record review of children (0-18 years) with a diagnosis of hypoglycemia (glucose ≤ 50 mg/dL) was performed. A comparison of results of critical sample (obtained during an episode of hypoglycemia) and fast-test (performed to induce hypoglycemia in fasting state) was done. RESULTS: In 317 patients with hypoglycemia, data of 89 critical samples and 52 fast-tests were taken. Only 7 (7.8%) patients who underwent critical sample testing received an endocrine or metabolic diagnosis. No confirmatory diagnoses were made using the fast-tests. Idiopathic ketotic hypoglycemia was detected in 33/89 (37.1%) of critical samples and 21/52 (40.4%) of fast-tests. The completeness of workup including the hormonal and metabolic profile was <80% in both tests. CONCLUSION: The confirmatory yield of critical sample was better than fast-test. The processing of metabolic analytes was incomplete in a few, suggesting the need to rationalize the dynamic function testing.

Stepwise genetic approach for the diagnosis of primary ciliary dyskinesia in highly consanguineous populations.

BACKGROUND: The American Thoracic Society guidelines for the diagnosis of primary ciliary dyskinesia (PCD) consider the presence of a bi-allelic pathogenic variant confirmatory for the diagnosis of PCD, with genetic testing recommended when other confirmatory diagnostic tests are less accessible. We present our experience with genetic testing as first line with a proposed algorithm for high consanguinity populations. METHODS: Patients with a suspected diagnosis of PCD underwent genetic testing according to a diagnostic algorithm composed of three steps: (1) patients with a previously known causative familial/Bedouin tribal pathogenic variant completed direct testing for a single variant; (2) if the initial test was negative or there was no known pathogenic variant, a PCD genetic panel was completed; (3) if the panel was negative, whole exome sequencing (WES) was completed. RESULTS: Since the implementation of the protocol, diagnosis was confirmed by genetic testing in 21 patients. The majority of them were of Bedouin origin (81%) and had a positive history of consanguinity (65%). Nine patients (43%) had a sibling with a confirmed diagnosis. Most patients (15/21, 71%) were diagnosed by direct pathogenic variant testing and the remainder by genetic panel (19%) and WES (10%). Disease-causing variants were found in nine genes, with DNAL1 (24%) and DNAAF3, DNAAF5, ZMYND10 (14% each) as the most prevalent ones. CONCLUSIONS: In highly consanguineous regions, a stepwise genetic testing approach is recommended. This approach may be particularly useful in areas where the ability to obtain confirmatory diagnostic tests through other modalities is less accessible.

Eradication of Nontuberculous Mycobacteria in People with Cystic Fibrosis Treated with Elexacaftor/Tezacaftor/Ivacaftor: A Multicenter Cohort Study.

BACKGROUND: The prevalence of nontuberculous mycobacteria (NTM) infections is rising in people with cystic fibrosis (pwCF). NTM infection, especially infection with Mycobacterium abscessus complex (MABC), is commonly associated with severe lung deterioration. The current treatment modalities, including multiple intravenous antibiotics, frequently fail to achieve airway eradication. Although treatment with elexacaftor/tezacaftor/ivacaftor (ETI) has been shown to modulate the lung microbiome, data regarding its role in eradicating NTM in pwCF is lacking. Our aim was to evaluate the impact of ETI on the rate of NTM eradication in pwCF. METHODS: This retrospective multicenter cohort study included pwCF from five CF centers in Israel. PwCF aged older than 6 who had at least one positive NTM airway culture in the past two years and were treated with ETI for at least one year were included. The annual NTM and bacterial isolations, pulmonary function tests, and body mass index were analyzed before and after ETI treatment. RESULTS: Fifteen pwCF were included (median age 20.9 years, 73.3% females, 80% pancreatic insufficient). In nine patients (66%) NTM isolations were eradicated following treatment with ETI. Seven of them had MABC. The median time between the first NTM isolation and treatment with ETI was 2.71 years (0.27-10.35 years). Eradication of NTM was associated with improved pulmonary function tests (p<0.05). CONCLUSIONS: For the first time, we report successful eradication of NTM, including MABC, following treatment with ETI in pwCF. Additional studies are needed to assess whether treatment with ETI can result in the long-term eradication of NTM.

Implementing a multiplex-PCR test for the diagnosis of acute gastroenteritis in hospitalized children: Are all enteric viruses the same?

BACKGROUND: Multiplex-PCR is a valuable tool for diagnosing viral acute gastroenteritis (AGE), enabling the detection of multiple pathogens. However, distinguishing between active disease and shedding poses challenges. This study aimed to evaluate viral AGE epidemiology and compare clinical characteristics among the five most common viruses. METHODS: Rotavirus vaccine was introduced in 2010, with 70% coverage achieved in southern Israel in two years. All rectal swabs for multiplex-PCR targeting rotavirus, norovirus, adenovirus, astrovirus and sapovirus from hospitalized diarrheic children <5 years were included, from December 2017 through March 2022. Detection of the same virus within two months was considered a single episode. Clinical analysis included episodes with single-virus detection and negative bacterial PCR. RESULTS: Among 5,879 rectal swabs, 2,662 (45.3%) tested positive for at least one virus, with 245 (9.2%) showing multiple virus detection. Rotavirus was the most prevalent. While rotavirus exhibited typical winter-spring seasonality in 2018-19, an unusual off-season surge was observed during the second year of the COVID-19 pandemic. Among negative bacterial PCR episodes, 34.6% had mucus stool, 5.9% had bloody stool, and 29.3% received antibiotics. Astrovirus or sapovirus infections were associated with higher rates of hospital-acquired AGE and immunodeficiency (P<0.05), whereas rotavirus infections had higher rates of dehydration severity and acute kidney injury (P<0.05). DISCUSSION: Enteric viruses were detected in 45.3% of rectal swabs from hospitalized children with diarrhea. Despite vaccination efforts, rotavirus remained prevalent and caused more severe disease. Continuous surveillance using multiplex-PCR is crucial for accurate management and future prevention strategies for viral AGE.

The role of anion gap normalization time in the management of pediatric diabetic ketoacidosis.

Introduction: Our aims were to determine whether anion gap normalization time (AGNT) correlates with risk factors related to the severity of diabetic ketoacidosis (DKA) in children, and to characterize AGNT as a criterion for DKA resolution in children admitted with moderate or severe disease. Methods: A ten-year retrospective cohort study of children admitted to the intensive care unit with DKA. We used a survival analysis approach to determine changes in serum glucose, bicarbonate, pH, and anion gap following admission. Using multivariate analysis, we examined associations between patients' demographic and laboratory characteristics with delayed normalization of the anion gap. Results: A total of 95 patients were analyzed. The median AGNT was 8 h. Delayed AGNT (>8 h) correlated with pH < 7.1 and serum glucose >500 mg/dL. In multivariate analysis, glucose >500 mg/dL was associated with an increased risk for delayed AGNT, by 3.41 fold. Each 25 mg/dL elevation in glucose was associated with a 10% increment in risk for delayed AGNT. Median AGNT preceded median PICU discharge by 15 h (8 vs. 23 h). Discussion: AGNT represents a return to normal glucose-based physiology and an improvement in dehydration. The correlation observed between delayed AGNT and markers of DKA severity supports the usefulness of AGNT for assessing DKA recovery.